IDE Related Topics

Pre-Clinical Studies and Good Laboratory Practices (GLP)

Overview

Good Laboratory Practices (GLP) under 21 CFR 58 applies to nonclinical laboratory studies (safety studies) that are intended to support applications for research and marketing permits including Investigational Device Exemption and Premarket Approval applications. Compliance with this part is intended to ensure the quality and integrity of safety data obtained from animal studies submitted to FDA.

If information on nonclinical laboratory studies is provided in the IDE application as part of the report of prior investigations, a statement that all such studies have been conducted in compliance with applicable requirements in the good laboratory practice regulations in part 58 must be provided. If any study was not conducted in compliance with the GLP regulations, a brief statement of the reason for the noncompliance must be provided. [§812.27]

Quality System Design Controls

Devices approved under an investigational device exemption (IDE) are exempt from the Quality System (QS) regulation, except for the design control requirements under §820.30. However, the sponsor may state an intention to comply with other parts of the QS regulation. The extent to which the Quality System regulation will be followed in manufacturing the device must be documented in the sponsor’s IDE records [§812.140(b)(4)(v)].

All manufacturers (or specification developers) of Class II and III devices, and Class I devices automated by computer software are required to follow design controls [§820.30] during the development of their device. A few Class I devices that are not automated by computer software are also subject to design controls. These devices are identified at 21 CFR § 820.30(a)(2)(ii).

The design control requirements are basic controls needed to ensure that the device being designed will perform as intended when produced for commercial distribution. Clinical evaluation is an important aspect of the design verification and validation process during the design and development of the device. Since most of the device design occurs prior to and during the IDE stage, it is necessary that manufacturers who intend to commercially produce the device follow design control procedures. If a manufacturer were to wait until the IDE studies were complete, it would be too late to take advantage of the design control process, and the manufacturer would not be able to fulfill design control requirements of the quality system regulation for that device.

The manufacturer or specification developer must establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met. Design controls include establishing and maintaining plans that describe the design and development activities and also define responsibility for implementation. The plans must identify and describe the interfaces with different groups or activities that provide, or result in, input to the design and development process.

Early in the design development process, design inputs or design requirements are identified. The design input should address topics such as user and patient needs, the intended use, performance characteristics, chemical and physical characteristics, safety, toxicity and biocompatibility, electromagnetic compatibility (EMC), reliability, regulatory requirements, historical data such as consumer complaints and MDRs, human factors, labeling and packaging, reliability, compatibility with accessories and auxiliary devices, compatibility with the environment of the intended use, risk analysis, voluntary standards, sterility, manufacturing processes, etc.

Although risk analysis is mentioned only in §820.30(g) Design validation, conducting risk analysis early in the design process enables designers to identify unreasonable risks and work to reduce or eliminate them during the early phases of design development. Conducting another risk analysis of the design toward the end of the design development process helps to identify any unreasonable risks that remain in the device or were introduced during design development.

Design reviews should be conducted periodically at major decision points during the design development process. Examples of major decision points are approval of the design input, completion of verification activities, and completion of validation activities. Design reviews are conducted to evaluate the adequacy of the design to meet requirements and also to identify problems with the design itself or the design process.

During the design process, the device design is verified and validated to assure that the design meets the users’ requirements. Design verification can be conducted at all stages and levels of design. Verification involves reviewing, inspecting, testing, checking, auditing or otherwise establishing whether or not components, subsystems, systems, the final device, processes, services, and documents conform to requirements or design inputs. Typical verification tests may include biocompatibility testing, risk analysis, package integrity testing, testing for conformance to standards, reliability testing, evaluating how well the product withstands sterilization, etc. Design validation ensures that the device meets the defined user needs and intended uses and includes testing of production units under simulated and/or actual use conditions. Clinical trials may be a part of the design validation process. Other methods of design validation include 510(k) historical database searches; literature searches; and review of labels, labeling, packaging, and other historical product information.

The IDE application is not required to include information regarding adherence to the design controls, and FDA does not inspect design controls during bioresearch monitoring inspections. However, procedures must be in place and documentation must be maintained in the design history file to demonstrate that the manufacturer is in compliance with the design control requirements of §820.30 and has carried out the activities identified in the design plan. The design history file must be made available for FDA inspection. FDA will evaluate the adequacy of manufacturers' compliance with design control requirements in pre-approval inspections for Class III devices and also during routine quality systems inspections for all classes of devices subject to design control.

Regulatory requirements for these products are in place to protect the public from hazardous or unnecessary radiation exposure emitted by these products. Requirements may include submission of reports to FDA, compliance with applicable radiation safety performance standards, retention of certain records, and reporting of accidental radiation occurrences or product defects to FDA. Additional information on requirements for radiation emitting products is available on the Radiological Health Program website.

Human Factors

Medical devices are used in many environments and often under adverse operating conditions. These issues affect the nature and complexity of the user interface. The interaction of the user's capabilities, the operating environment, and device user interface will determine the extent to which a device is used safely and effectively.

The QS regulation requires manufacturers to address the user interface of the equipment during device design and development. The user interface includes all aspects of a device (including its labeling) that users see, feel and hear when operating the device.

The user interface needs of health professionals and lay or untrained users of medical devices are addressed in design input and are confirmed through design validation during the IDE stage of development.

"Human factors" is the study of the interaction of people and machines to ensure the safety and effectiveness of that interaction. The discipline encompasses various methods used to improve human/equipment compatibility, including the user interface, user instructions, and training programs to avoid user error. Human factors consideration is critical to ensuring proper design and is best done by systematic consideration of human factors in the development of the device user interface.